Burn wounds may be classified into four categories of increasing depth: superficial, intermediate partial thickness, deep partial thickness, and full thickness. The latter two classifications typically require aggressive interventions that involve the debridement of necrotic tissue and the application of split thickness skin grafts. These are more morbid wounds typically wrought with the potential for hypertrophic scarring and contractures and may necessitate early surgical excision and grafting to optimize the outcome, See e.g., Ryan et al., Objective Estimates of the Probability of Death From Burn Injuries, N. Engl. J. Med., 1998, 338: 362-6, incorporated by reference herein. Selecting the level of debridement sufficient to minimize inflammation and determining the optimal treatment in a timely fashion is critical given the risks of infection and sepsis. The success of grafting depends on the removal of virtually all necrotic tissue and any biofilm and requires the presence of highly-vascularized granulation tissue. The goal of early debridement for grafting is to remove all the devitalized tissue for skin grafting until only granulation tissue remains. Using a conventional tissue excision procedure, several layers of burned tissue are excised until the viable wound bed is reached, as evidenced by capillary bleeding. See e.g., Orgill et al., Excision and Skin Grating Of Thermal Burns, New England Journal of Medicine, 2009, Feb. 26; 360(9): 893-901, incorporated by reference herein. Although bleeding is typically assumed to mean the tissue is viable, this conventional tissue excision procedure is subjective and imprecise because it relies on visual inspection that does not preclude the possibility that some necrotic tissue or biofilm will be inadvertently left in the wound site.
Given the challenges in objectively determining tissue viability, a number of conventional technologies have been repurposed with the intent of providing metrics of tissue viability, such as Laser Doppler Imaging (LDI) and Indocyanine green angiography (ICG).
Conventional LDI is a highly recognized noninvasive technique for clinical evaluation of burn wound and tissue viability assessment. Several conventional LDI devices are available which estimate the blood flow in the area of interest. See e.g., Jaskille et al., Critical Review of Burn Depth Assessment Techniques: Part II, Review of Laser Doppler Technology, Journal of Burn Care & Research, 2010, Jan. 1; 31(1):151-7, incorporated by reference herein. However, LDI has several drawbacks. Because flowmetry requires the probe to directly contact with the burn wound, it may increase the risk of wound infection and may inflict trauma to already vulnerable tissue. See e.g., O'Reilly et al., Laser Doppler Flowmetry Evaluation of Burn Wound Depth, Journal of Burn Care & Research, 1989, Jan. 1; 10(1):1, incorporated by reference herein. Additionally, because LDI measures perfusion in one spot at the time, assessing a large burn wound may be a time-consuming process. Additionally, there is some risk that LDI may not detect necrotic tissue in the wound bed. See e.g., Atiles et al., Laser Doppler Flowmetry In Burn Wounds, Journal of Burn Care & Research, 1995, Jul. 1; 16(4): 388-93, incorporated by reference herein.
Conventional Indocyanine green (ICG) video-angiography provides greater skin imaging penetration compared to LDI. ICG enables visualization of the deep dermal vasculature using a dye. See e.g., Jerath et al., Burn Wound Assessment in Porcine Skin Using Indocyanine Green Fluorescence, Journal of Trauma and Acute Care Surgery, 1999, Jun. 1; 46(6): 1085-8, incorporated by reference herein. ICG is based on the fluorescent properties of the dye being used and quantifying the intensity of the dye. ICG provides color-coded maps relative to the perfusion of the investigated area. The major drawback associated with conventional ICG video-angiography is that intravascular dye injection is required. Previous studies have shown a high degree of association between headache, pruritus, urticarial and anaphylactic reaction following the dye injection. See e.g., Benya et al., Adverse Reactions to Indocyanine Green: A Case Report and a Review of the Literature. Catheterization and Cardiovascular Diagnosis, 1989, Aug. 1; 17(4):231-3, incorporated by reference herein.
While conventional LDI and ICG each offer a unique approach to detecting tissue viability, both techniques are cumbersome to manipulate in a surgical setting, have a large size, and do not provide for real-time diagnosis, critical for tissue viability assessment during an excision procedure.